Diego Simeone's side must face Los Che ahead of its Champions League semifinal second leg against Chelsea at Stamford Bridge.
Atletico Madrid faces a huge test in its quest for trophies as it begins a run of three crucial games in the space of a week at Valencia.
La Liga leader Atleti travels to the Mestalla with a four-point cushion over reigning champion Barcelona, while city rival Real is two further behind in third, though it has a game in hand.
Following Sunday's encounter, Diego Simeone's men travel to Chelsea for their Champions League semifinal second leg, with the tie at 0-0 after the first encounter, and a trip to Levante rounds off a testing seven days.
The capital club deserves credit for challenging the domestic dominance of Barca and Real this season, and three points would see it inch ever closer to the Primera Division title.
The Vincente Calderon side is protecting an eight-match winning streak in the league, a sequence during which its defense has been breached just once.
This fixture has been earmarked as a potential banana skin for the visitors. Valencia has lost just one of their last eight league matches on home soil.
Rojiblancos can take confidence from a 3-0 victory in the reverse fixture this campaign, though the corresponding encounter last season saw Valencia triumph 2-0.
The sides have also met in Copa del Rey action this year, with Madrid progressing from its round-of-16 tie 3-1 on aggregate after a 1-1 draw in Valencia.
With all the ingredients in place for a classic encounter, Atleti goalkeeper Thibaut Courtois insists the squad is fully prepared to face Juan Antonio Pizzi's men.
He told the club's official website: "As we go game-by-game our biggest test now is Valencia. We're at a good level physically. I think we're good, we can make one more effort on the field and that's good for the remaining games. Our first final is on Sunday.
"We have seen in the Copa it will be a tough game, you have to play it as a final and only if we do so, can we move forward."
Atleti will be hoping Pizzi's charges are still licking their wounds from a 2-0 setback at Sevilla in the Europa League semifinal first leg, a result that leaves its place in the tournament in jeopardy ahead of Thursday's return tie.
Center back Philippe Senderos (knock) could join goalkeeper Diego Alves (hamstring) and defensive duo Ricardo Costa (ankle) and Victor Ruiz (thigh) in missing out, while Atleti will monitor the fitness of winger Arda Turan who has only recently returned following a groin injury.